title: Mechanisms involved in the beneficial effects of spironolactone after myocardial infarction.
abstract: BACKGROUND
  Our objective was to analyze the effect of spironolactone on cardiac remodeling after experimental myocardial infarction (MI), assessed by matricellular proteins levels, cardiac collagen amount and distribution, myocardial tissue metalloproteinase inhibitor-1 (TIMP-1) concentration, myocyte hypertrophy, left ventricular architecture, and in vitro and in vivo cardiac function.
  
  
  METHODS
  Wistar rats were assigned to 4 groups: control group, in which animals were submitted to simulated surgery (SHAM group; n=9); group that received spironolactone and in which animals were submitted to simulated surgery (SHAM-S group, n=9); myocardial infarction group, in which animals were submitted to coronary artery ligation (MI group, n=15); and myocardial infarction group with spironolactone supplementation (MI-S group, n=15). The rats were observed for 3 months.
  
  
  RESULTS
  The MI group had higher values of left cardiac chambers and mass index and lower relative wall thicknesses compared with the SHAM group. In addition, diastolic and systolic functions were worse in the MI groups. However, spironolactone did not influence any of these variables. The MI-S group had a lower myocardial hydroxyproline concentration and myocyte cross-sectional area compared with the MI group. Myocardial periostin and collagen type III were lower in the MI-S group compared with the MI-group. In addition, TIMP-1 concentration in myocardium was higher in the MI-S group compared with the MI group.
  
  
  CONCLUSIONS
  The predominant consequence of spironolactone supplementation after MI is related to reductions in collagens, with discrete attenuation of other remodeling variables. Importantly, this effect may be modulated by periostin and TIMP-1 levels.
authors.affiliation: Internal Medicine Department, Botucatu Medical School, University Estadual Paulista, Botucatu, São Paulo, Brazil.
authors.forename: Marcos F
authors.initials: MF
authors.lastname: Minicucci
authors.forename: Priscila P
authors.initials: PP
authors.lastname: dos Santos
authors.forename: Bruna P M
authors.initials: BP
authors.lastname: Rafacho
authors.forename: Andrea F
authors.initials: AF
authors.lastname: Gonçalves
authors.forename: Renata A C
authors.initials: RA
authors.lastname: Silva
authors.forename: Fernanda
authors.initials: F
authors.lastname: Chiuso-Minicucci
authors.forename: Paula S
authors.initials: PS
authors.lastname: Azevedo
authors.forename: Bertha F
authors.initials: BF
authors.lastname: Polegato
authors.forename: Katashi
authors.initials: K
authors.lastname: Okoshi
authors.forename: Elenize J
authors.initials: EJ
authors.lastname: Pereira
authors.forename: Sergio A R
authors.initials: SA
authors.lastname: Paiva
authors.forename: Leonardo A M
authors.initials: LA
authors.lastname: Zornoff
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D001837:Body Weights and Measures; D003094:Collagen / Q000187:drug effects* / Q000378:metabolism; D004452:Echocardiography; D006909:Hydroxyproline / Q000378:metabolism; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology*; D032342:Muscle Cells / Q000187:drug effects; D009203:Myocardial Infarction / Q000188:drug therapy*; D051381:Rats; D017208:Rats, Wistar; D013148:Spironolactone / Q000494:pharmacology*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D016277:Ventricular Function, Left / Q000187:drug effects; D020257:Ventricular Remodeling / Q000187:drug effects*
chemical_list: D000451:Mineralocorticoid Receptor Antagonists; D019715:Tissue Inhibitor of Metalloproteinase-1; D013148:Spironolactone; D003094:Collagen; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D006909:Hydroxyproline